Shaping the future of probiotics, live biotherapeutic products, and fecal microbiota transplantation: 30 scientific recommendations from the CHINAGUT Conference

The 2025 CHINAGUT Conference has assembled a panel of 63 experts (30 scientists, 26 physicians, and 7 corporate R&D personnel) collaborated in three groups to present 30 scientific recommendations to advance probiotics, live biotherapeutic products, and fecal microbiota transplantation, addressing key issues on standardization, translation, supervision, regulation, and regulatory harmonization. These interdisciplinary guidelines aim to synthesize cutting-edge knowledge and practical needs to transform microbiota-based treatments from applications into precision-driven medical solutions, and serve as reference by scientific researchers, medical educators, pharmaceutical enterprises, clinicians, food and drug administrations, policymakers, and patients. The development of microbiome-based medical and healthcare industries constitutes as a globally recognized interdisciplinary frontier, demonstrating transformative potential for the prevention, diagnosis, and treatment of systemic disorders—including infections, inflammatory conditions, and immune-mediated diseases involving multiple organs [1]. Over the past decade, probiotic science and industry, live biotherapeutic products (LBPs), and the translational applications of fecal microbiota transplantation (FMT) have garnered widespread global attention. During the 2025 CHINAGUT Conference, an expert panel officially released 30 scientific recommendations to holistically promote the sustainable translational and industrial development in these fields (Figure 1). The CHINAGUT Conference is a premier academic conference with global leadership. Established in 2014 and formally launched under its current name in 2018, it spans clinical medicine, pharmaceutics, veterinary medicine, food science, and the health industries. It serves as a platform for establishing authoritative position statements, expert consensus, and clinical practice guidelines. The 2025 CHINAGUT Conference specifically highlighted recent advancements in microbiome technologies and microbiota medicine. Over 5000 professionals in the gut and related fields from Asia, Europe, North America, and Australia participated in the conference. The conference featured 54 academic, translational, and career development sessions, with nearly 500 researchers presenting 528 academic reports and showcasing 1213 posters on site. For the 2025 CHINAGUT Conference, a distinguished core expert panel was convened to develop interdisciplinary scientific recommendations. Twenty experts to propose 10 scientific recommendations for promoting the high-quality development of probiotic science and food industry; 20 experts to formulate 10 scientific recommendations for advancing the development of LBPs; and 26 experts to establish 10 scientific recommendations for facilitating the translational application and sustainable development of FMT. Some recommendations from the expert panel were established through a Delphi voting process. Collectively, the expert panel brings together 30 scientists, 26 clinicians, and 7 corporate R&D personnel from 29 cities, representing 28 scientific research institutions, 22 hospitals, and 7 innovative enterprises in China. These recommendations fully integrate cutting-edge advancements and practical needs across research, development, ethics, regulation, and governmental oversight, providing crucial expert perspectives, reference frameworks, and implementation guidelines to shape the future of these microbiota-based treatments. These recommendations are intended for reference by scientific researchers, medical educators, pharmaceutical companies, clinicians, food and drug administrations, policymakers, and patients. Contributed by Wei Chen, Ping Li, Canhui Lan, Wei Li, Chaoxin Man, Yonghui Ma, Huayi Suo, Zhihong Sun, Guangqiang Wang, Xin Wang, Rina Wu, Zhen Wu, Xiang Xiao, Huaxi Yi, Qixiao Zhai, Liang Zhao, Guohua Zhang, Heping Zhang, Jiachao Zhang, and Wenyi Zhang. Probiotics are live microorganisms which when administered in adequate amounts confer a health benifit on the host. As a medical product, probiotics typically require more stringent regulation and evidence-based support. Despite rapid market expansion, they face persistent challenges in strain identification, safety assessment, health benefit validation, and quality control. The absence of standardized strain identification protocols has led to inconsistent product quality, complicating consumer differentiation between effective and substandard products. Additionally, multi-strain formulations are frequently developed empirically rather than through evidence-based approaches, lacking rigorous assessment of strain interactions. Safety concerns are particularly acute for immunocompromised populations, where comprehensive risk evaluation remains inadequate. These shortcomings negatively impact market credibility and constrain long-term industry growth. At the 2025 CHINAGUT Conference, an expert panel addressed these issues and formulated 10 recommendations to improve product quality, enhance market competitiveness, and foster sustainable development of the probiotic sector. Prioritization: short-term goals achievable within 1 to 3 years. Precise strain-level identification is the cornerstone of probiotic science and industrial development, directly impacting product safety, efficacy, and stability. Whole-genome sequencing (WGS) should be adopted as the gold standard for strain identification, comprehensively characterizing the genus, species, subspecies, and unique strain designation, linked to internationally recognized culture collections (e.g., ATCC or DSMZ) and published research data. Identification must encompass phenotypic and genotypic traits, screening for safety-related genes (e.g., antibiotic resistance genes) and functional properties. Strains should be deposited in internationally accredited repositories, adhering to the International Code of Nomenclature of Prokaryotes to eliminate multiple designations for the same strain. Establishing unified standards for strain identification and nomenclature can effectively address issues of standardization deficiencies, disordered development, and insufficient evidence, enhancing quality control of Chinese probiotic products and global competitiveness. Prioritization: long-term objectives spanning 3 to 5 years. The market for multi-strain probiotic formulations is rapidly expanding, yet current combination strategies often rely excessively on empirical or market-driven approaches, lacking theoretical support. To enhance the efficacy and reliability of probiotic formulations, strain combination strategies should be optimized based on scientific evidence. Combinations must have clear objectives, prioritizing functionally complementary strains, with synergistic or antagonistic effects systematically evaluated through in vitro coculture and in vivo animal or human studies. Strain combinations should be validated through high-quality randomized controlled trials (RCTs) to ensure overall efficacy, with dose–response studies determining optimal combination ratios and stability [2]. The industry should establish a public database of strain combinations, systematically investigating metabolic networks and ecological dynamics to provide data support for scientific combinations, promoting standardization and high-quality development of probiotic formulations. Prioritization: immediate priorities requiring action within 1 year. Comprehensive strain-level safety assessments are a prerequisite for advancing probiotic science and industry, tailored to strain characteristics, intended uses, and target populations, particularly immunocompromised or vulnerable groups. Key steps include: confirming strain identity and genetic background via WGS; referencing safety frameworks such as the EU Qualified Presumption of Safety or U.S. Generally Recognized as Safe lists, supplemented by strain-specific reviews [3]; mandatory screening for transferable antibiotic resistance genes, evaluating virulence factors and potentially harmful metabolic activities; and conducting toxicological studies when necessary to confirm non-pathogenicity. Safety claims must be supported by rigorous data specific to the application context, particularly for vulnerable populations. Prioritization: short-term goals achievable within 1 to 3 years. The evaluation of probiotic health benefits must adopt high-quality, double-blind, placebo-controlled RCTs as the gold standard to address the industry's challenge of insufficient evidence. RCT designs should adhere to the following principles: clearly defined hypotheses and target populations; adequate sample sizes to ensure conclusive results; appropriate randomization and blinding; suitable placebo controls; well-characterized interventions (strain, dose, viability); clinically relevant and validated outcome measures; and sufficient trial duration with follow-up. All trials must comply with international ethical guidelines, such as the Declaration of Helsinki, and domestic regulations, including the Administrative Measures for Ethical Review of Biomedical Research Involving Humans issued by the Chinese government. Studies must undergo review by an independent ethics committee to ensure the scientific and ethical integrity of the study protocol, guarantee fully informed consent, and protect participants' rights and interests. For vulnerable populations—such as pregnant women, infants, young children, the elderly, and individuals with compromised immune systems—ethical reviews must place special emphasis on informed consent and the protection of their rights, given their limited decision-making autonomy. All trials must be pre-registered on public platforms (e.g., China Clinical Trial Registry, ChiCTR), with results transparently reported regardless of outcome. The industry should transition from fragmented, small-scale studies to large-scale, rigorously designed RCTs to meet regulatory requirements for high-standard health claims. Prioritization: short-term goals achievable within 1 to 3 years. The effective dosage of probiotics is specific to the strain and health condition, and higher doses are not necessarily more effective. Recommended doses, typically ranging from N × 107 to N × 1010 colony-forming units (CFU) per day, must be supported by reliable scientific evidence demonstrating efficacy for specific strains and health outcomes, rather than arbitrary values or an excessive focus on high viable counts. Doses exceeding this range require clinical data support or guidance from clinicians based on individual health conditions. For healthy individuals, higher doses may not provide additional benefits. The goal is to determine the minimum effective dose. For safe strains, while no scientifically established upper safety limit exists, the key consideration is whether higher doses offer additional benefits compared to lower, validated effective doses, while accounting for cost-effectiveness. Dose-ranging studies are ideal. Product labels must clearly indicate the viable count (CFU) of each strain at the end of shelf life. For multi-strain formulations, particular attention should be given to the proportionality of each strain. Prioritization: short-term goals achievable within 1 to 3 years. The efficacy of probiotic products depends on ensuring microbial viability and stability throughout production, storage, and shelf life. The industry must fully adopt Good Manufacturing Practices (GMP) and establish standardized viability testing methods to ensure product quality consistency and comparability. Key factors include production processes, product matrices, packaging technologies, storage conditions, and gastrointestinal survival. Optimization strategies include: selecting robust strains; refining production processes; employing microencapsulation or protective agents; combining with prebiotics to enhance viability; and adding sufficient initial counts to compensate for storage losses. Real-time stability studies and reliable viable count methods are critical for validating shelf-life viability, with particular focus on the stability of strain ratios in multi-strain formulations. Prioritization: immediate priorities requiring action within 1 year. Standardized labeling and marketing communications are essential for the healthy development of the probiotic industry. Product labels must provide accurate, transparent, and non-misleading information, including: complete strain identification (genus, species, strain designation); viable count (CFU) at the end of shelf life; recommended serving size and storage conditions; scientifically validated health benefit claims with a clear indication of the level of supporting evidence (e.g., RCT evidence or animal study evidence); mandatory warnings for vulnerable populations (e.g., "Individuals with compromised immune function should consult a physician before use"); expiration date; and manufacturer contact information. Marketing communications must avoid exaggerated or misleading claims strictly prohibiting the use of absolute terms such as "cure" or "complete recovery," and clearly distinguish probiotics from general fermented foods. To curb false advertising, companies engaging in violations should face product recalls, public disclosure of violations, and high fines, while consumers should be encouraged to monitor and report misleading claims to maintain market integrity. The industry should establish ethical marketing guidelines, encourage third-party certifications to enhance consumer trust, and strictly comply with Chinese food labeling regulations to elevate industry credibility. Prioritization: long-term objectives spanning 3 to 5 years. Regulatory frameworks for probiotics vary across countries and regions and are continually evolving. Companies must proactively track and comply with Chinese regulations (State Administration for Market Regulation, the National Health Commission, and GB standards) and international guidelines (e.g., FAO/WHO definitions, EFSA scientific opinions, FDA dietary supplement regulations), covering strain identification, safety, efficacy validation, and health claims. FAO/WHO provides foundational probiotic definitions, EFSA imposes stringent health claim requirements, FDA regulates dietary supplements, and Chinese health food regulations specify requirements for strain identification and functional evaluation. Companies should develop targeted strategies, particularly for new strain approvals through China's "Three New Foods" pathway, to ensure product compliance and support scientifically validated health claims. Prioritization: long-term objectives spanning 3 to 5 years. Industry-academia-research partnerships are critical for technological breakthroughs and industrial advancement in probiotics, bridging the gap between fundamental research and product development. Collaborations must be based on clear agreements, uphold scientific integrity, and ensure commercial interests do not compromise research independence. Collaborative research must disclose funding sources and any potential conflicts of interest, and corporate sponsors must not interfere with study design, data analysis, or the publication of results to ensure that commercial interests do not distort scientific conclusions, such as through selective publication of positive findings. Industry associations should play a coordinating role, developing collaboration guidelines, promoting best practices, and organizing cross-institutional efforts to address shared technical challenges, such as developing validated biomarkers. By pooling resources for large-scale, high-quality trials, these partnerships can enhance research credibility and translation efficiency, fostering a continuous innovation ecosystem to advance industry technology and market competitiveness. At the same time, it is encouraged that industry associations collaborate with experts in medicine, ethics, and law to establish independent ethics committees to provide ongoing oversight of strain safety claims, health benefit communications, and industry-academia-research collaborations. Prioritization: long-term objectives spanning 3 to 5 years. Establishing a science-based public education system is a core strategy for enhancing public understanding and promoting sustainable development of the probiotic industry. Educational content must be grounded in evidence-based data, covering the scientific definition of probiotics, strain-specific principles, label interpretation methods, and validated health benefits, using standardized terminology to ensure accuracy and consistency. For healthcare professionals, systematic training should focus on evidence-based efficacy, dosage recommendations, and potential risks of specific strains to support informed clinical decision-making. Industry associations and scientific institutions should collaborate to establish authoritative education platforms, integrating high-quality research data to ensure scientific accuracy. Companies must align marketing content with educational materials, avoiding exaggerated claims. Through multi-stakeholder collaboration, public scientific literacy on probiotics can be systematically enhanced, fostering informed consumption, strengthening market trust, and incentivizing sustained investment in research and standardized development. Although the establishment of a standardized strain identification system is recommended, in practice, the varying regulatory requirements across different countries and regions—may significantly hinder the standardization process. Optimizing strain combination strategies and validating health benefits require extensive fundamental research and clinical trials, which are not only time-consuming and labor-intensive but also necessitate financial support and interdisciplinary collaboration. In summary, the advancement of probiotic science and industry requires systematic improvements in multiple areas, including standardization, safety evaluation, health benefit validation, quality control, and market education (Figure 2). By implementing 10 scientific recommendations, current challenges can be effectively addressed to promote high-quality industry development. In the future, with technological advancements and strengthened international cooperation, the probiotic industry is expected to achieve sustainable development globally, providing stronger support for public health. Contributed by Lei Cheng, Lei Dai, Meng Guo, Changtao Jiang, Xianzhi Jiang, Canhui Lan, Shuangjiang Liu, Hongwei Liu, Xingyin Liu, Yonghui Ma, Yan Tan, Wanyi Tao, Jun Wang, Xin Wang, Ye Wang, Bin Xiang, Jun Yu, Chenhong Zhang, Fangqing Zhao, Hongwei Zhou, and Shu Zhu. In recent years, LBPs have emerged as a promising therapeutic strategy, garnering significant attention for their potential to modulate the host microbiota and elicit therapeutic benefits. However, the underlying mechanisms of action for many LBPs remain poorly understood, complicating rational drug design, targeted patient selection, and regulatory evaluation. Moreover, the design of LBP clinical trials is further complicated by the lack of standardized biomarkers for patient stratification and efficacy assessment. Additionally, the manufacturing processes for LBPs are complex, with significant challenges in quality control and high production costs. These challenges are further compounded by the unique difficulties associated with LBPs, such as the cultivation of strictly anaerobic bacteria, the determination of concentration and dosing, and the barriers to achieving efficient production. The expert panel at the 2025 CHINAGUT Conference proposed 10 scientific recommendations aimed at advancing the clinical translation and widespread application of LBPs. Prioritization: long-term objectives spanning 3 to 5 years. Currently, the mechanisms of action (MoA) of many LBPs remain poorly understood, posing challenges to rational drug design, targeted patient selection, and regulatory evaluation. The focus of future research should shift from correlation analysis to mechanistic investigation, identifying specific functional factors, metabolic pathways, and host receptors/pathways targeted by LBPs. Gnotobiotic animal models, organoids, multi-omics, and systems biology are needed to clarify the molecular and cellular mechanisms of LBPs, where human-relevant mechanisms cannot be sufficiently modeled otherwise [4], such as host-microbe interactions, microbial metabolites, and immune regulation, etc. For lower-risk applications, validated alternatives such as ex vivo intestinal models should be considered to balance scientific rigor with feasibility. Advancing mechanistic research requires breakthroughs in underlying technologies, such as functional prediction and genome editing of non-model microorganisms, with particular attention to functional variability among strains within the same species. Then, validate mechanistic hypotheses with actual dosing in early clinical trials, establishing causal chains through dynamic monitoring of patients' microbiomes and host responses. A clear understanding of the MoA can reduce development risk, enable strain selection based on specific targets, and enhance the predictive capability of animal models. It also allows the inclusion of mechanism-based biomarkers in clinical trials, facilitates regulatory approval, improves physician acceptance, and increases the likelihood of payer reimbursement. Prioritization: long-term objectives spanning 3to 5 years. Due to the differences in individual microbiomes and immune responses between host organisms, traditional animal models often fail to accurately predict the human efficacy of LBPs. The lack of predictive preclinical models is a major reason for the high attrition rate in LBP clinical trials. Improved models can help candidate selection, dosing optimization, and early safety identification, thereby increasing clinical success rates. Research should focus on models that can study LBP colonization, persistence, functional activity, and interaction with the host immune system in a human-relevant manner. Advanced ex vivo, in vitro, and in vivo preclinical models should be developed to mimic human gut (or other sites, such as the vagina, skin, etc.) physiology, dysbiosis, and disease states. Humanized microbiota animal models, gut-on-a-chip systems, and complex coculture systems have shown promising applications in this regard. Prioritization: long-term objectives spanning 3 to 5 years. Implement adaptive and innovative double-blind clinical trial designs with meaningful, objective endpoints, and stratify patients using biomarkers to enhance trial efficiency and success. Biomarkers with preliminary validation require confirmation of their predictive value through independent clinical cohort validation. LBP trials are challenged by microbiota variability and disease complexity, making "one-size-fits-all" approaches ineffective. Endpoints should be robust and reflect real patient benefits. Grouping patients based on baseline microbiome characteristics, immune response, host metabolism, host genetics, or other biomarkers helps identify patient subgroups that are most likely to respond to LBPs. Developing predictive biomarkers is critical for enabling personalized LBPs and improving trial outcomes. Prioritization: short-term goals achievable within 1 to 3 years. Under conditions that permit, systematically integrate artificial intelligence (AI) and machine learning (ML) with multi-omics technologies to accelerate LBP discovery, optimize development, and enable personalized therapeutic strategies. The diverse microbiota and host–microbe interactions generate massive datasets including genomics, transcriptomics, proteomics, and metabolomics. AI/ML is adept at analyzing these large datasets, and can be used to predict the phenotypes of newly isolated strains, elucidate the molecular and cellular mechanisms of unreported strains, identify novel therapeutic targets, predict LBP efficacy, discover biomarkers for patient stratification, optimize formulations and simplify production processes [5, 6]. This data-driven approach is essential for next-generation LBPs. AI/ML is a potentially transformative tool to overcome the challenges of complexity and variability in LBP development. For example, ML-based modeling can be used to predict and design high-yield butyrate-producing microbial consortia for disease treatment. Prioritization: long-term objectives spanning 3 to 5 years. A key aspect of the chemistry, manufacturing, and controls (CMC) strategy for LBPs is the use of live bacteria with different physiological characteristics in various dosage forms tailored for different routes of administration, such as oral, topical, or injectable. CMC development strategies should be designed according to the needs of each development stage, including preclinical, early-stage clinical, late-stage clinical, and commercialization. Overcome challenges related to the production of live microorganisms (often anaerobic), such as fermentation, stability, and exogenous factors. Conduct research on critical quality attributes and develop appropriate quality standards. Pay close attention to strain stability, potency testing, formulation stability, and cost-effective large-scale manufacturing under GMP conditions. Innovation in characterization and potency assay methods is essential. QbD (Quality by Design) and PAT (Process Analytical Technology) approaches help ensure product consistency and quality. For engineered strains, it is necessary to establish a genetic stability monitoring system and design biosafety switches to prevent environmental release. Prioritize strategies for genetic stability that focus on homologous recombination over plasmid-based expression to minimize mutation rates. Design Boolean circuits, such as AND/OR gates, integrating environmental sensors (e.g., temperature, pH, metabolites), as practical guidance. Prioritization: short-term goals achievable within 1 to 3 years. Ensure early and continuous communication with regulatory agencies (e.g., FDA, CDE, EMA, NMPA) to seek clear guidance, contribute to guideline development, and advocate for the establishment of a coordinated, science-based regulatory framework that suits the unique nature of LBPs. LBPs have the potential to enter the environment and healthy individuals. Clinical trials should consider potential bioleakage risks and establish biosafety control strategies. The regulatory landscape for LBPs is evolving, and specific requirements remain to be clarified. Engineered bacteria based on patient-specific characteristics offer an effective approach for personalized live-bacterial therapy. Currently, there is a lack of relevant standards for clinical trials involving genetically engineered bacteria. Supportive policies and clear industry standards are needed to promote clinical research on live engineered bacterial therapeutics. Active dialog can help address LBP-specific challenges such as potency assays, stability requirements, safety evaluation of new microbial strains and nonclinical testing strategies. Promoting international harmonization through platforms such as ICH can reduce duplication and facilitate global development. Industry associations and scientific institutions can play a vital role in building consensus standards and best practices to guide regulatory approaches. A clear and predictable regulatory pathway encourages investment and accelerates LBP development. Prioritization: immediate priorities requiring action within 1 year. The LBP field is particularly unsuitable for traditional isolated R&D approaches. Collaboration can pool resources, share risks, and accelerate learning. Actively establish and participate in pre-competitive collaborations and public-private partnerships to share knowledge, resources, and risks, thereby accelerating the research and development of LBPs. The complexity of LBP development requires expertise and capabilities from different fields—academic institutions promote drug discovery and the understanding of drug mechanisms, biotechnology companies carry out process innovation and early-stage development, large pharmaceutical companies provide resources for late-stage trials and commercialization, CROs/CDMOs offer professional services. regulatory agencies provide guidance and patient advocacy groups provide insights and support. Pre-competitive collaborations can address common challenges such as biomarker validation, development of standardized analytical methods, or creation of shared data resources without compromising the competitive interests of companies. Prioritization: long-term objectives spanning 3 to 5 years. Develop a comprehensive strategy in the early stage of the development process to demonstrate the clinical and economic value of LBPs to payers, physicians, and patients, as well as to promote the integration of LBPs into the existing healthcare system. Market access is a major barrier for LBPs. Securing reimbursement and physician adoption poses significant challenges for LBPs. Demonstrating value requires not only robust clinical evidence (efficacy and safety) but also health economic outcomes, clear data on whether they improve patients' quality of life, and comparisons with existing standard treatments. Educating healthcare providers on the mechanisms, efficacy, safety, and appropriate use of LBPs is crucial to overcoming skepticism and improving accurate patient selection. Early engagement with payers to understand their evidence requirements and establish suitable pricing and reimbursement models is essential. A proactive, evidence-based market access strategy is equally important as scientific development. Prioritization: short-term goals achievable within 1 to 3 years. As an em